Thyroid malignant peripheral nerve sheath tumors (TMPNST) are very uncommon neoplasms that can be confused with anaplastic carcinoma, Riedel's thyroiditis, or other soft tissue tumors that may occur in the thyroid region. An example of TMPNST is presented in this report. The tumor occurred in a 56-yr-old woman. Fine needle aspiration did not provide adequate material. After thyroidectomy, the lesion posed important problems in differential diagnosis. Immunohistochemical, molecular, and electron microscopic features were taken into consideration to arrive at the correct diagnosis. Tumor cells were focally positive for keratins, a feature that has not been described in peripheral nerve sheath tumors of the thyroid, but that has been occasionally seen in tumors from other locations. After thyroidectomy, the patient received radiotherapy. She is well without evidence of recurrence 10 mo after surgery.